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Tocotrienol inhibits proliferation of human Tenon's fibroblasts in vitro: a comparative study with vitamin E forms and mitomycin C

Meyenberg, Alexander ; Goldblum, David ; Zingg, Jean-Marc ; Azzi, Angelo ; Nesaretnam, Kalanithi ; Kilchenmann, Monika ; Frueh, Beatrice

In: Graefe's Archive for Clinical and Experimental Ophthalmology, 2005, vol. 243, no. 12, p. 1263-1271

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    Titre
    • Tocotrienol inhibits proliferation of human Tenon's fibroblasts in vitro: a comparative study with vitamin E forms and mitomycin C
    Auteur
    • Meyenberg, Alexander. Departement of Ophthalmology, University of Berne, Inselspital Berne, 3010, Berne, Switzerland
    • Goldblum, David. Departement of Ophthalmology, University of Berne, Inselspital Berne, 3010, Berne, Switzerland
    • Zingg, Jean-Marc. Institute for Biochemistry and Molecular Biology, University of Berne, Buehlstrasse 28, 3012, Berne, Switzerland
    • Azzi, Angelo. Institute for Biochemistry and Molecular Biology, University of Berne, Buehlstrasse 28, 3012, Berne, Switzerland
    • Nesaretnam, Kalanithi. Malaysian Palm Oil Board, PO Box 10620, 50720, Kuala Lumpur, Malaysia
    • Kilchenmann, Monika. Departement of Ophthalmology, University of Berne, Inselspital Berne, 3010, Berne, Switzerland
    • Frueh, Beatrice. Departement of Ophthalmology, University of Berne, Inselspital Berne, 3010, Berne, Switzerland
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • Graefe's Archive for Clinical and Experimental Ophthalmology, 2005, vol. 243, no. 12, p. 1263-1271. Springer-Verlag
    Autre version électronique
    Classification
    • Santé
    Identifiant OAI-PMH
    • oai:doc.rero.ch:315322
    Summary
    Purpose: To evaluate the potential of the vitamin E compound α-tocotrienol as antifibrotic agent in vitro. Methods: Using human Tenon's capsule fibroblast cultures, the antiproliferative and cytotoxic effects of the different vitamin E forms α-tocopherol, α-tocopheryl acetate, α-tocopheryl succinate and α-tocotrienol were compared with those of mitomycin C. To mimic subconjunctival and regular oral application in vivo, exposure time of serum-stimulated and serum-restimulated fibroblasts (SF and RF, respectively) to vitamin E forms was set at 6 days. Cultures were only exposed for 5min to mitomycin C due to its known acute toxicity and to mimic the short-time intraoperative administration. Proliferation (expressed as % of control) was determined by DNA content quantification on days 2, 4 and 6, whereas cytotoxicity was assessed by cell morphology and glucose 6-phosphate dehydrogenase (G6PD) release after 24h. Results: α-Tocopherol and α-tocopheryl acetate stimulated growth of SF, but not RF. Reduction of fibroblast content by α-tocopheryl succinate was accompanied by increased G6PD release and necrosis. Contrary to α-tocopheryl succinate, 50μM or repeatedly 20μM of α-tocotrienol significantly inhibited proliferation without causing cellular toxicity (maximal effect: 46.8%). RF were more sensitive to this effect than SF. Mitomycin C 100-400μg/ml showed a stronger antiproliferative effect than α-tocotrienol (maximal effect: 13.8%). Morphologic characteristics of apoptosis were more commonly found under treatment with mitomycin C. Conclusions: Of the vitamin E forms tested, only α-tocotrienol significantly inhibited growth at non-toxic concentrations. In this in vitro study, antiproliferative effects of mitomycin C were stronger than those of α-tocotrienol